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Protein

Fumarate hydratase class II

Gene

fumC

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the reversible addition of water to fumarate to give L-malate.1 Publication

Catalytic activityi

(S)-malate = fumarate + H2O.1 Publication

Enzyme regulationi

Inhibited by ATP and S-2,3-dicarboxyaziridine.1 Publication

Kineticsi

  1. KM=50 µM for L-malate (at pH 7.3 and 30 degrees Celsius)1 Publication

    pH dependencei

    Optimum pH is 8.1 Publication

    Pathway:itricarboxylic acid cycle

    This protein is involved in step 1 of the subpathway that synthesizes (S)-malate from fumarate.
    Proteins known to be involved in this subpathway in this organism are:
    1. Fumarate hydratase class I, aerobic (fumA), Fumarate hydratase class II (fumC)
    This subpathway is part of the pathway tricarboxylic acid cycle, which is itself part of Carbohydrate metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes (S)-malate from fumarate, the pathway tricarboxylic acid cycle and in Carbohydrate metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei188 – 1881Proton donor/acceptorBy similarity
    Active sitei318 – 3181By similarity
    Binding sitei319 – 3191SubstrateBy similarity
    Sitei331 – 3311Important for catalytic activity

    GO - Molecular functioni

    • fumarate hydratase activity Source: EcoCyc

    GO - Biological processi

    • fumarate metabolic process Source: InterPro
    • response to oxidative stress Source: EcoCyc
    • tricarboxylic acid cycle Source: UniProtKB-HAMAP
    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Biological processi

    Tricarboxylic acid cycle

    Enzyme and pathway databases

    BioCyciEcoCyc:FUMC-MONOMER.
    ECOL316407:JW1603-MONOMER.
    MetaCyc:FUMC-MONOMER.
    BRENDAi4.2.1.2. 2026.
    SABIO-RKP05042.
    UniPathwayiUPA00223; UER01007.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Fumarate hydratase class II (EC:4.2.1.2)
    Short name:
    Fumarase C
    Alternative name(s):
    Iron-independent fumarase
    Gene namesi
    Name:fumC
    Ordered Locus Names:b1611, JW1603
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    ProteomesiUP000000318 Componenti: Chromosome UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10358. fumC.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi126 – 1261R → A: Reduces enzyme activity 10-fold. 1 Publication
    Mutagenesisi127 – 1271K → D: No effect. 1 Publication
    Mutagenesisi129 – 1291H → N: No effect on activity, but the carboxyamide group from Asn129 swings into the B site and replaces S-malate by forming a bifurcated hydrogen bond with Asn131 and Asp132. 2 Publications
    Mutagenesisi188 – 1881H → N: Reduces activity 200-fold. 1 Publication
    Mutagenesisi315 – 3151E → Q: Reduces activity 10-fold. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 467467Fumarate hydratase class IIPRO_0000161275Add
    BLAST

    Proteomic databases

    PaxDbiP05042.
    PRIDEiP05042.

    Expressioni

    Inductioni

    Under conditions of iron limitation and oxidative stress.1 Publication

    Interactioni

    Subunit structurei

    Homotetramer.6 Publications

    Protein-protein interaction databases

    DIPiDIP-9719N.
    IntActiP05042. 14 interactions.
    STRINGi511145.b1611.

    Structurei

    Secondary structure

    1
    467
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi5 – 95Combined sources
    Beta strandi12 – 165Combined sources
    Helixi24 – 329Combined sources
    Helixi42 – 6120Combined sources
    Helixi67 – 8115Combined sources
    Turni82 – 854Combined sources
    Helixi86 – 883Combined sources
    Beta strandi92 – 954Combined sources
    Helixi100 – 11718Combined sources
    Helixi130 – 1345Combined sources
    Turni135 – 1373Combined sources
    Helixi140 – 15819Combined sources
    Helixi160 – 17718Combined sources
    Turni178 – 1803Combined sources
    Beta strandi182 – 1876Combined sources
    Beta strandi190 – 1967Combined sources
    Helixi197 – 22226Combined sources
    Turni230 – 2323Combined sources
    Helixi242 – 25413Combined sources
    Helixi264 – 2696Combined sources
    Helixi272 – 29827Combined sources
    Beta strandi302 – 3054Combined sources
    Beta strandi308 – 3103Combined sources
    Helixi328 – 35225Combined sources
    Helixi362 – 38625Combined sources
    Helixi388 – 3903Combined sources
    Helixi395 – 40410Combined sources
    Helixi406 – 4083Combined sources
    Helixi409 – 4135Combined sources
    Turni414 – 4163Combined sources
    Helixi418 – 43114Combined sources
    Helixi435 – 4417Combined sources
    Helixi447 – 4537Combined sources
    Helixi456 – 4583Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FUOX-ray1.98A/B1-467[»]
    1FUPX-ray2.30A/B1-467[»]
    1FUQX-ray2.00A/B1-467[»]
    1FURX-ray1.95A/B1-467[»]
    1KQ7X-ray2.60A/B1-467[»]
    1YFEX-ray2.19A1-467[»]
    2FUSX-ray2.20A/B1-467[»]
    ProteinModelPortaliP05042.
    SMRiP05042. Positions 4-459.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP05042.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni98 – 1003Substrate binding
    Regioni129 – 1324B site
    Regioni139 – 1413Substrate binding
    Regioni187 – 1882Substrate bindingBy similarity
    Regioni324 – 3263Substrate bindingBy similarity

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0114.
    HOGENOMiHOG000061736.
    InParanoidiP05042.
    KOiK01679.
    OMAiIEKDTMG.
    OrthoDBiEOG6V1M4M.
    PhylomeDBiP05042.

    Family and domain databases

    Gene3Di1.10.275.10. 1 hit.
    HAMAPiMF_00743. FumaraseC.
    InterProiIPR005677. Fum_hydII.
    IPR024083. Fumarase/histidase_N.
    IPR018951. Fumarase_C_C.
    IPR020557. Fumarate_lyase_CS.
    IPR000362. Fumarate_lyase_fam.
    IPR022761. Fumarate_lyase_N.
    IPR008948. L-Aspartase-like.
    [Graphical view]
    PANTHERiPTHR11444. PTHR11444. 1 hit.
    PfamiPF10415. FumaraseC_C. 1 hit.
    PF00206. Lyase_1. 1 hit.
    [Graphical view]
    PRINTSiPR00149. FUMRATELYASE.
    SUPFAMiSSF48557. SSF48557. 1 hit.
    TIGRFAMsiTIGR00979. fumC_II. 1 hit.
    PROSITEiPS00163. FUMARATE_LYASES. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P05042-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MNTVRSEKDS MGAIDVPADK LWGAQTQRSL EHFRISTEKM PTSLIHALAL
    60 70 80 90 100
    TKRAAAKVNE DLGLLSEEKA SAIRQAADEV LAGQHDDEFP LAIWQTGSGT
    110 120 130 140 150
    QSNMNMNEVL ANRASELLGG VRGMERKVHP NDDVNKSQSS NDVFPTAMHV
    160 170 180 190 200
    AALLALRKQL IPQLKTLTQT LNEKSRAFAD IVKIGRTHLQ DATPLTLGQE
    210 220 230 240 250
    ISGWVAMLEH NLKHIEYSLP HVAELALGGT AVGTGLNTHP EYARRVADEL
    260 270 280 290 300
    AVITCAPFVT APNKFEALAT CDALVQAHGA LKGLAASLMK IANDVRWLAS
    310 320 330 340 350
    GPRCGIGEIS IPENEPGSSI MPGKVNPTQC EALTMLCCQV MGNDVAINMG
    360 370 380 390 400
    GASGNFELNV FRPMVIHNFL QSVRLLADGM ESFNKHCAVG IEPNRERINQ
    410 420 430 440 450
    LLNESLMLVT ALNTHIGYDK AAEIAKKAHK EGLTLKAAAL ALGYLSEAEF
    460
    DSWVRPEQMV GSMKAGR
    Length:467
    Mass (Da):50,489
    Last modified:August 13, 1987 - v1
    Checksum:i3D67E3C0F0FDF40B
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X04065 Genomic DNA. Translation: CAA27698.1.
    U00096 Genomic DNA. Translation: AAC74683.1.
    AP009048 Genomic DNA. Translation: BAA15349.1.
    X00522 Genomic DNA. Translation: CAA25205.1.
    PIRiS07138. UFEC.
    RefSeqiNP_416128.1. NC_000913.3.
    WP_001099085.1. NZ_CP010445.1.

    Genome annotation databases

    EnsemblBacteriaiAAC74683; AAC74683; b1611.
    BAA15349; BAA15349; BAA15349.
    GeneIDi946147.
    KEGGieco:b1611.
    PATRICi32118524. VBIEscCol129921_1682.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X04065 Genomic DNA. Translation: CAA27698.1.
    U00096 Genomic DNA. Translation: AAC74683.1.
    AP009048 Genomic DNA. Translation: BAA15349.1.
    X00522 Genomic DNA. Translation: CAA25205.1.
    PIRiS07138. UFEC.
    RefSeqiNP_416128.1. NC_000913.3.
    WP_001099085.1. NZ_CP010445.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FUOX-ray1.98A/B1-467[»]
    1FUPX-ray2.30A/B1-467[»]
    1FUQX-ray2.00A/B1-467[»]
    1FURX-ray1.95A/B1-467[»]
    1KQ7X-ray2.60A/B1-467[»]
    1YFEX-ray2.19A1-467[»]
    2FUSX-ray2.20A/B1-467[»]
    ProteinModelPortaliP05042.
    SMRiP05042. Positions 4-459.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    DIPiDIP-9719N.
    IntActiP05042. 14 interactions.
    STRINGi511145.b1611.

    Proteomic databases

    PaxDbiP05042.
    PRIDEiP05042.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC74683; AAC74683; b1611.
    BAA15349; BAA15349; BAA15349.
    GeneIDi946147.
    KEGGieco:b1611.
    PATRICi32118524. VBIEscCol129921_1682.

    Organism-specific databases

    EchoBASEiEB0353.
    EcoGeneiEG10358. fumC.

    Phylogenomic databases

    eggNOGiCOG0114.
    HOGENOMiHOG000061736.
    InParanoidiP05042.
    KOiK01679.
    OMAiIEKDTMG.
    OrthoDBiEOG6V1M4M.
    PhylomeDBiP05042.

    Enzyme and pathway databases

    UniPathwayiUPA00223; UER01007.
    BioCyciEcoCyc:FUMC-MONOMER.
    ECOL316407:JW1603-MONOMER.
    MetaCyc:FUMC-MONOMER.
    BRENDAi4.2.1.2. 2026.
    SABIO-RKP05042.

    Miscellaneous databases

    EvolutionaryTraceiP05042.
    PROiP05042.

    Family and domain databases

    Gene3Di1.10.275.10. 1 hit.
    HAMAPiMF_00743. FumaraseC.
    InterProiIPR005677. Fum_hydII.
    IPR024083. Fumarase/histidase_N.
    IPR018951. Fumarase_C_C.
    IPR020557. Fumarate_lyase_CS.
    IPR000362. Fumarate_lyase_fam.
    IPR022761. Fumarate_lyase_N.
    IPR008948. L-Aspartase-like.
    [Graphical view]
    PANTHERiPTHR11444. PTHR11444. 1 hit.
    PfamiPF10415. FumaraseC_C. 1 hit.
    PF00206. Lyase_1. 1 hit.
    [Graphical view]
    PRINTSiPR00149. FUMRATELYASE.
    SUPFAMiSSF48557. SSF48557. 1 hit.
    TIGRFAMsiTIGR00979. fumC_II. 1 hit.
    PROSITEiPS00163. FUMARATE_LYASES. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Structural and functional relationships between fumarase and aspartase. Nucleotide sequences of the fumarase (fumC) and aspartase (aspA) genes of Escherichia coli K12."
      Woods S.A., Miles J.S., Roberts R.E., Guest J.R.
      Biochem. J. 237:547-557(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    4. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
      Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
      Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    5. "Complete nucleotide sequence of the fumarase gene fumA, of Escherichia coli."
      Miles J.S., Guest J.R.
      Nucleic Acids Res. 12:3631-3642(1984) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-89.
    6. "The fumarase genes of Escherichia coli: location of the fumB gene and discovery of a new gene (fumC)."
      Guest J.R., Miles J.S., Roberts R.E., Woods S.A.
      J. Gen. Microbiol. 131:2971-2984(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-89.
    7. "Purification and characterization of two types of fumarase from Escherichia coli."
      Ueda Y., Yumoto N., Tokushige M., Fukui K., Ohya-Nishiguchi H.
      J. Biochem. 109:728-733(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-20, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBUNIT.
    8. "Purification and crystallization of fumarase C from Escherichia coli."
      Weaver T.M., Levitt D.G., Banaszak L.J.
      J. Mol. Biol. 231:141-144(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-15, SUBUNIT.
    9. "Two biochemically distinct classes of fumarase in Escherichia coli."
      Woods S.A., Shwartzbach S.D., Guest J.R.
      Biochim. Biophys. Acta 954:14-26(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOCHEMICAL ANALYSIS OF FUMA AND FUMC, SUBUNIT.
    10. "Oxygen, iron, carbon, and superoxide control of the fumarase fumA and fumC genes of Escherichia coli: role of the arcA, fnr, and soxR gene products."
      Park S.J., Gunsalus R.P.
      J. Bacteriol. 177:6255-6262(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    11. "Escherichia coli proteome analysis using the gene-protein database."
      VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.
      Electrophoresis 18:1243-1251(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY 2D-GEL.
    12. "The role of the allosteric B site in the fumarase reaction."
      Rose I.A., Weaver T.M.
      Proc. Natl. Acad. Sci. U.S.A. 101:3393-3397(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ARG-126; LYS-127 AND HIS-129.
    13. "Aspartase/fumarase superfamily: a common catalytic strategy involving general base-catalyzed formation of a highly stabilized aci-carboxylate intermediate."
      Puthan Veetil V., Fibriansah G., Raj H., Thunnissen A.M., Poelarends G.J.
      Biochemistry 51:4237-4243(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: REACTION MECHANISM.
    14. "Crystallographic studies of the catalytic and a second site in fumarase C from Escherichia coli."
      Weaver T., Banaszak L.
      Biochemistry 35:13955-13965(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS), SUBUNIT.
    15. "Mutations of fumarase that distinguish between the active site and a nearby dicarboxylic acid binding site."
      Weaver T., Lees M., Banaszak L.
      Protein Sci. 6:834-842(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF MUTANTS ASN-129 AND ASN-188 IN COMPLEX WITH MALATE AND CITRATE, MUTAGENESIS OF HIS-129 AND HIS-188.
    16. "X-ray crystallographic and kinetic correlation of a clinically observed human fumarase mutation."
      Estevez M., Skarda J., Spencer J., Banaszak L., Weaver T.M.
      Protein Sci. 11:1552-1557(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF MUTANT GLN-315, MUTAGENESIS OF GLU-315, SUBUNIT.
    17. "Structure of free fumarase C from Escherichia coli."
      Weaver T.
      Acta Crystallogr. D 61:1395-1401(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS).

    Entry informationi

    Entry nameiFUMC_ECOLI
    AccessioniPrimary (citable) accession number: P05042
    Secondary accession number(s): P76891
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: August 13, 1987
    Last modified: July 22, 2015
    This is version 155 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    There are 2 substrate-binding sites: the catalytic A site, and the non-catalytic B site that may play a role in the transfer of substrate or product between the active site and the solvent. Alternatively, the B site may bind allosteric effectors.

    Keywords - Technical termi

    3D-structure, Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.